Development of gene-activated matrices as tools in new regenerative therapies

  1. Rilo Alvarez, Héctor
Supervised by:
  1. Marcos García Fuentes Director
  2. Anxo Vidal Figueroa Director

Defence university: Universidade de Santiago de Compostela

Year of defence: 2024

Committee:
  1. Rosa María Hernández Martín Chair
  2. Luis Antonio Díaz Gómez Secretary
  3. María del Carmen Arufe Gonda Committee member
Department:
  1. Department of Pharmacology, Pharmacy and Pharmaceutical Technology

Type: Thesis

Teseo: 828438 DIALNET lock_openMINERVA editor

Abstract

The main goal of this thesis has been the development, optimization, and testing of three-dimensional mRNA-activated matrices as a system for the administration of transcription factors for articular cartilage regeneration. Modifications in the mRNA synthesis provided higher stability and efficacy as compared to standard mRNA. TAMs chondrogenic effects were tested in 3D cultures activated with SOX9, TGF-β3 or combinations of both. The transcript combination provided the best effects as it combined the strong chondrogenic effect of TGF-β3 with the capacity of SOX9 to promote chondroblast differentiation while inhibiting fibrotic tissue formation. The two best TAM prototypes were studied in a cartilage defect rabbit model where showed no signs of toxicity and promoted the expression of specific tissue markers.